This is the first study investigating the clinical relevance of 5-hydroxymethylcytosine (5hmC) in genomic DNA from white blood cells (WBC) in the context of prostate cancer (PCa) and other prostate pathologies. Using an enzyme-linked immunosorbent assay, we identified significantly different distributions of patients with low and elevated 5hmC content in WBC DNA across controls and patients with prostate cancer (PCa), atypical small acinar proliferation (ASAP), and benign prostatic hyperplasia (BPH). The measured values were within the normal range for most PCa patients, while the latter category was predominant for ASAP. We observed a wider heterogeneity in 5hmC content in all of the prostate pathologies analyzed when compared to the healthy age-matched controls. When compared to blood levels of prostate-specific antigen (PSA), this 5hmC-based biomarker had a lower performance in PCa detection than the use of a PSA cut-off of 2.5 nanograms per milliliter (ng/mL). Above this threshold, however, it delineated almost three quarters of PCa patients from controls and patients with other prostate pathologies. Overall, genome-wide 5hmC content of WBC DNA appears to be applicable for detecting non-cancerous prostate diseases, rather than PCa. Our results also suggest a potential clinical usefulness of complementing PSA as a PCa marker by the addition of a set of hydroxymethylation markers in the blood, but further studies are necessary to confirm these findings.

We report two siblings with congenital generalized hypertrichosis and distinctive facial appearance consistent with the dysmorphic facial features described in Ambras syndrome. The patients were born to non-consanguineous, phenotypically normal parents. This is the first report of affected siblings and could be explained by either autosomal recessive inheritance or by germline mosaicism for an autosomal dominant gene. We compared the phenotype of our patients to descriptions of reported cases and discuss phenotypic variability.

This is a fatal case of multiple complicated congenital anomalies displaying several symptoms consistent with hydrolethalus syndrome. The newborn’s phenotype is characterized by a combination of serious anatomical abnormalities such as open-book cerebral hemispheres, defective lobulation of the lungs (one lobe on the left, two on the right), a smaller right kidney, a smooth cerebral surface, and a specific keyhole-shaped defect in the skull base, primarily associated with hydrocephalus.

Background and Clinical Significance : Adams–Oliver syndrome type 3 (AOS3) is a rare congenital disorder typically characterised by terminal transverse limb defects and variable involvement of other organ systems. Although pathogenic variants in RBPJ are well established in AOS3, associated neurodevelopmental or psychiatric features have been only sporadically documented. Case Presentation: We describe a male patient first evaluated at the age of 10 years and subsequently re-evaluated at 14 years, with AOS3 presenting terminal limb defects together with autistic-like behaviour, cognitive difficulties, dyslexia, and recurrent depressive symptoms. Whole-exome sequencing (WES) identified a heterozygous pathogenic variant in RBPJ (c.505A>G; p.Lys169Glu), confirming the molecular diagnosis of autosomal dominant AOS3. Additional findings included a heterozygous missense variant in CACNA1A (p.Arg1678Cys), a gene linked to neurological disorders with broad phenotypic variability. Because of elevated homocysteine levels, the patient was also tested for MTHFR variants and was found to be heterozygous for C677T and A1298C. Conclusions: This case illustrates a rare combination of a validated AOS3-associated RBPJ variant, along with additional CACNA1A and MTHFR variants that may influence the patient’s neurocognitive and psychiatric characteristics. The results underscore the importance of comprehensive genetic testing in atypical AOS presentations and highlight the complexity of interpreting overlapping genetic factors.